The invention relates to radioactive medical devices. More specifically, the invention relates to radioactive medical devices which may be used in radiation therapy of diseased tissue.
Radiation therapy is used extensively to treat diseased tissue such as cancers and especially malignant tumors. The goal of radiation therapy is to destroy the diseased or malignant tissue without causing excessive damage to nearby healthy tissue. One form of radiation therapy involves directing one or more beams of radiation from a point external to a subject""s body into the area in which the tumor, malignant cells or diseased tissue, is located. Unfortunately, the beam of radiation must pass through healthy tissue to reach the diseased target tissue.
Another type of radiation therapy involves the delivery of a radioactive source directly to the site of diseased tissue. These methods include, for example, the use of a catheter, the surgical implantation of one or more radioactive seeds, or the injection of one or more seeds into the patient in close proximity to the diseased tissue.
Prior art radioactive sources typically have a radioactive element affixed to a substrate, and the radioactive substrate covered with a bio-compatible sealing layer to prevent leaching of the radioactive element into the patient. For example, U.S. Pat. No. 5,938,604 discloses a needle comprising an electroplated radioactive metal (Tc99m) that is covered with additional layers of plating to prevent subsequent removal of the radioactive material. Similarly, U.S. Pat. No. 5,405,309 teaches electroplating a Palladium-103/ Palladium admixture onto a pellet of electroconductive material and further electroplating the pellet with a bio-compatible container or shell, such as titanium. A major limitation of the teachings of these patents is that the outer plating layers absorb a significant amount of radiation emitted from the radioactive inner plating layer requiring that high levels of radioactivity must be deposited on the inner layer to compensate for the radiation attenuation by the outer plating layer. The deposition of higher levels of radioactivity on the inner plating layer is costly. Further, the substrates are electroplated first with a radioactive element and then electroplated again or sealed within a bio-compatible container or shell. These methods are complex and expensive, and introduce the possibility of increasing the risk to workers during the second electroplating step.
U.S. Pat. No. 4,323,055 to Kubiatowicz, discloses that chemisorbtion of I-125 onto a silver layer, and these coated seeds are then sealed within a titanium container in order to effectively control the migration of I-125 from the seed. However, the use of a titanium outer shell results in substantial attenuation of the outer protective layer. U.S. Pat. No. 4,323,055 discloses radioactive seeds for use in radiation therapy of diseased tissue. The seed comprises a sealed container having a therapeutic amount of radioactive iodine distributed on a carrier body. The carrier body is disposed in a cavity of a tubular titanium container which is sealed at both ends. Radioactive iodine is attached to a silver substrate by first chloriding or bromiding the silver to form a layer of insoluble silver chloride or silver bromide and then replacing the chloride or bromide ions by simple ion exchange. Unfortunately, the level of radioactivity incorporated must be increased to compensate for the 14% attenuation in the radiation field by the titanium container. The incorporation of increased levels of radioactivity to compensate for the attenuation by the container is costly. U.S. Pat. No. 3,351,049 also relates to radioactive seeds comprising a central body coated with a radioisotope that is sealed in a container. In one embodiment, the container is constructed of a metal of a low atomic number, such as stainless steel alloy or titanium. However, as disclosed within the patent, the attenuation of stainless steel is about 15% per thousandth of an inch while the attenuation for titanium is about 5% per thousandth of an inch, and additional radioisotope must be added to compensate for absorption losses in the container walls. It is noted that I-125 seeds require a metallic seal to prevent leaching of I-125 from the substrate, again significantly attenuating the amount of radiation emmnited from the seed. An analogous approach is disclosed in U.S. Pat. No.3,811,426 that comprises depositing Pu-238 onto a wire. The radioisotope layer is covered with a coating layer such as platinum. Both the radioactive layer and the coating layer are applied by electrolytic processes such as sputter deposition. Again, the coating layer attenuates the radiation emitted by the radioactive layer of the wire. Also, the two electroplating processes make the radioactive wire more difficult and more expensive to make than radioactive wires comprising a single electroplating step and an easy and inexpensive coating step. Furthermore, wires that are electroplated or electrosputtered exhibit little or no flexibility.
U.S. Pat. No. 5,713,828 discloses a brachytherapy device formed from a hollow, tube-shaped substrate on which a radioactive source is disposed. The radioactive seed is sealed in a sealing layer comprising an organic coating such as polypropylene, polyethylene terephthalate, nylon, polyurethane or a bio-compatible metal or metal compound. The disclosed brachytherapy device must be of dimensions which allows a support material such as a surgical thread to be threaded through the hollow tube of the device. Thus the brachytherapy device is limited as to its minimum diameter. Further, it is well known in the art that certain radioactive elements such as iodine are not easily retained on substrates because of their volatility. The above-identified patent contemplates coating substrates with iodine-125 according to the chemisorbtion method disclosed in U.S. Pat. No. 4,323,055 (Kubiatoicz), however, an I-125 coated substrate sealed in a single sealing layer as taught in U.S. Pat. No. 5,713,828 may allow leaching of significant amounts of radioactive I-125 within a patient. Since it is well known that iodine accumulates in the thyroid gland in humans, the smallest amount of I-125 leaching from the disclosed brachytherapy device could severely compromise the health of a patient. A similar method is disclosed in U.S. Pat. No. 5,163,896 which comprises coating a tungsten rod or pellet with a radioactive-absorbing binder material to which a radioactive material is adsorbed. The radioactive rod is encapsulated with a coating material which seals the pellet. The pellet may be encapsulated in a container made of material other than titanium provided that the container material does not substantially inhibit irradiation from the seed, and provided that the material is resistant to corrosion by body fluids. This method is generally not applicable with the use of volatile radioactive elements such as I-125 which would leach from the binder material over prolonged periods.
U.S. Pat. No. 5,342,283 (Good) relates to radioactive implants and a method for making radioactive implants. The patent teaches incorporating a radioactive element into a seed, ribbon or wire, and subsequently coating the radioactive layer with other coating layers comprising a metal diffusion barrier (for example titanium, tantalum, gold, platinum, tungsten carbide) and a bio-compatible protective coat including metal (e.g. titanium), or diamond or diamond-like carbon. The diffusion barrier and protective coat are deposited on the radioactively coated substrate by sputtering, laser-ablation ion plating, or cathodic arc plasma deposition. The diffusion barrier and the protective coat may absorb significant amounts of radiation emitted from the radioactive inner plating layer and therefore high levels of radioactivity must be deposited prior to being coated with the diffusion and outer plating layers, which is costly. Thus, these implants are more difficult and costly to produce than implants which require a single electroplating step and an easy and inexpensive coating step for their manufacture.
Canadian patent application CA 2,010,038 relates to production and use of Yb-168 or Yb-169 seeds and wires via neutron bombardment. These radioactive substrates may comprise an outer coating of titanium, aluminum, PTFE-coated aluminum or other plastic. There is no disclosure of seeds comprising other isotopes.
There is a need in the art for radioactive, electroplated substrates of high activity and substantially uniform radioactivity that are both easy and inexpensive to manufacture. Further, there is a need for radioactive, electroplated substrates that are coated and sealed with layers of material that reduce leaching of the radioactive element from the substrate, yet are minimize attenuation of the radiation so that the layers of material do not substantially absorb the radiation emitted from the substrate. There is also a need for radioactive substrates having coating or sealing layers which do not impart excessive bulk to the radioactive substrate or alter the tensile properties, such as pliablility or malleability of the substrate.
It is an object of the present invention to overcome drawbacks of the prior art.
The above object is met by a combination of the features of the main claims. The sub claims disclose further advantageous embodiments of the invention.
The present invention relates to radioactive medical devices. More specifically, the invention relates to radioactive medical devices useful for radiation therapy of diseased tissue.
According to the present invention, there is provided a radioactive medical device comprising a radioactive, electroplated substrate coated with at least one layer of polymer and sealed in a jacket layer.
The present invention also relates to a radioactive medical device as described above wherein the substrate is formed entirely of metal, or partially of a metal. The substrate may be silver and have the shape of a wire. The radioactive medical device may be a stent, wire or a seed.
The present invention also relates to radioactive medical devices as described above electroplated with a radioactive element that may be selected from the group consisting of P-32, S-35, Cl-36, Sc-47, Cu-67, Y-90, Mo-99, Pd-103, Sn-117m, I-123, I-124, I-125, I-129, -131, Ce-144, Ho-166, Re-186, Re-188, W-188, Ir-192, and Au-199.
The present invention also relates radioactive medical devices as described above having from 1 to about 10 layers of polymer. The polymer may be selected from the group consisting of polyurethane polypropylene, polysulfone, polyphenylsulfone, polyethersulfone, polyimide, VITON, nylon, polyester/polyolefins, ceramics, PVP, cellulose.
The present invention also relates to a method of manufacturing a radioactive medical device coated with at least one layer of polymer and sealed in a jacket layer, comprising the steps of;
a) electroplating a substrate with a radioactive element to form a radioactive, electroplated substrate;
b) coating the radioactive-electroplated substrate in at least one layer of polymer to form a radioactive, electroplated substrate coated with at least one layer of polymer and;
c) sealing the radioactive, electroplated substrate coated with at least one layer of polymer in a jacket layer.
The present invention also relates to the use of the radioactive medical device as defined above for delivery of radiation to diseased tissue. Further, the radioactive medical device may be used for brachytherapy or for restenosis.
This summary does not necessarily describe all necessary features of the invention but that the invention may also reside in a sub-combination of the described features.